Products of manufacture comprising bacteriophages

Patent metadata

Field	Value
Publication number	US-11260089-B2
Application number	US-201515528354-A
Country	US
Kind code	B2
Filing date	Nov 18, 2015
Priority date	Nov 19, 2014
Publication date	Mar 1, 2022
Grant date	Mar 1, 2022

Abstract

Provided are compositions and methods for treating, ameliorating and preventing various infections, disorders and conditions in mammals, including genetically-predisposed and chronic disorders, where a microbial or bacterial flora is at least one causative or symptom-producing factor, where exemplary compositions are products of manufacture, a food, a drink, a nutraceutical, a dietary supplement, a formulation, a pharmaceutical or a pharmaceutical preparation comprising at least one or several of a plurality of isolated, or substantially purified bacteriophages or prophages, or bacteriophage subunits, a milk, a milk product, milk lipid, milk fat globule (MFG) macromolecule, a milk mucin, a milk glycolipid, a milk free glycan, a milk mucin-like glycoprotein, a milk protein, a milk sugar or lactose, a milk fat or butterfat, a milk vitamin. In alternative embodiment, provided are compositions and methods for treating, preventing or ameliorating an infection, for example, an infection in the gastrointestinal tract, or bowel.

First claim

What is claimed is:

1. A composition comprising:
a plurality of isolated, or substantially purified intact Caudovirales bacteriophages adherent or bound to mucins or negatively charged glycans on a surface of:
(i) an isolated or substantially purified: milk lipid, milk fat globule (MFG) macromolecule, or a mixture thereof;
(ii) an isolated plasma membrane, or component of a plasma membrane,
(iii) a hydrogel,
(iv) a biocompatible crosslinked degradable thiol-ene polymer, or
(v) any combination thereof,
by binding or adhering to the mucins or negatively charged glycans,
wherein all of (i) to (iv) comprise and express on their surfaces the mucins or negatively charged glycans.

2. The composition of claim 1 , wherein the Caudovirales bacteriophage are formulated per dose, or per serving, or per unit dosage at, or at a total daily dose of: between about 10 1 and 10 20 plaque-forming units (PFUs), or between about 10 3 and 10 17 PFUs, or between about 10 5 and 10 12 PFUs, or between about 10 7 and 10 9 PFUs.

3. The composition of claim 1 , further comprising a pharmaceutically acceptable excipient.

4. The composition of claim 1 , formulated for administration in vivo; or for enteral or parenteral administration, or for ophthalmic, topical, oral, intranasal, intrarectal, intravaginal, intravenous, intra-peritoneal, intraocular, intra-placental, intra-bladder, cutaneous, intravenous (IV), intramuscular (IM), intrathecal, subcutaneous (SC), intracerebral, epidural, intracranial or rectal administration, or by inhalation.

5. The composition of claim 1 , formulated or manufactured as or placed or formulated into:
(a) a tablet, a pill, a capsule, a gel, a geltab, a liquid, a powder, a suspension, a syrup, an emulsion, a lotion, an ointment, an aerosol, a spray, a lozenge, an ophthalmic preparation, an aqueous or a sterile or an injectable solution, or a patch, wherein optionally the patch is a transdermal patch or a medicated adhesive patch,
(b) an implant, a dietary supplement, an ice cream, an ice, a yogurt, a cheese, an infant formula or infant dietary supplement, a pasteurized milk or milk product or milk-comprising product; or
(c) a veterinary formulation or feed.

6. The composition of claim 1 , further comprising, or having added to:
a flavoring or a sweetening agent, an aspartamine, a stevia , monk fruit, a sucralose, a saccharin, a cyclamate, a xylitol, a vanilla, an artificial vanilla or chocolate or strawberry flavor, an artificial chocolate essence, or a mixture or combination thereof;
a preservative, a benzoic acid, a potassium sorbate;
at least one probiotic or prebiotic, wherein optionally the prebiotic comprises an inulin, lactulose, extracts of artichoke, chicory root, oats, barley, various legumes, garlic, kale, beans or flacks or an herb,
at least one congealing agent, wherein optionally the congealing agent comprises an arrowroot or a plant starch, a powdered flour, a powdered potato or potato starch, an absorbant polymer, an ABSORBABLE MODIFIED POLYMER® (AMP®), a corn flour or a corn starch;
at least one anti-inflammatory agent, wherein optionally the at least one inflammatory agent comprises or is an NSAID, a 4 or a 5-amino-salicylate, an olsalazine, a mesalazine, a sulfasalazine, a balsalazide, or an equivalent thereof or a combination thereof; or
an additive selected from one or more of a saline, a media, a defoaming agent, a surfactant agent, a lubricant, an acid neutralizer, a marker, a cell marker, a drug, an antibiotic, a contrast agent, a dispersal agent, a buffer or a buffering agent or a pharmaceutically acceptable excipient, a sweetening agent, a debittering agent, a flavoring agent, a pH stabilizer, an acidifying agent, a preservative, a desweetening agent and/or coloring agent, vitamin, mineral and/or dietary supplement, an antacid or a prebiotic nutrient,
and optionally the buffer or a buffering agent or the pharmaceutically acceptable excipient comprises an inorganic salt, a citric acid, a sodium chloride, a potassium chloride, a sodium sulfate, a potassium nitrate, a sodium phosphate monobasic, a sodium phosphate dibasic or combinations thereof,
and optionally the antacid comprises a calcium carbonate, a magnesium hydroxide, a magnesium oxide, a magnesium carbonate, an aluminum hydroxide, a sodium bicarbonate or a dihydroxyaluminum sodium carbonate; or any combination thereof.

7. The composition of claim 1 , wherein the composition is isolated, treated, formulated or prepared as a delayed or gradual enteric release composition.

8. The composition of claim 1 , wherein the isolated, or substantially purified milk fat globule (MFG) macromolecule has a particle size between about: 1 nm to 100 nm, 100 nm to 1000 nm, 1 um to 100 um, or 100 um to 1000 um.

9. The composition of claim 1 , wherein the isolated, or substantially purified milk fat globule (MFG) macromolecule comprises between about 0.01% to 1%, or between about 1% to 20% of the composition.

10. A delivery vehicle, a product of manufacture, a container, a syringe, device or an implant, comprising: the composition of claim 1 .

11. A liquid, a suspension, a gel, a geltab, a semisolid, a tablet, a sachet, a lozenge or a capsule, a freeze-dried composition, an infant formula, or an enteral or parenteral formulation, comprising: the composition of claim 1 .

12. The composition of claim 1 , wherein the isolated, or substantially purified milk lipid or milk fat globule (MFG) macromolecule is derived from a mammalian milk.

13. The composition of claim 1 , wherein the plasma membrane, or component of a plasma membrane:
(a) is reconstituted as a globular particle of a specific size range,
and optionally the globular particle has a size of between about: 1 nm to 100 nm, 100 nm to 1000 nm, 1 um to 100 um, or 100 um to 1000 um; or
(b) is a bacterial plasma membrane, or component of a bacterial plasma membrane.

14. The composition of claim 3 , wherein the composition comprises:
an antibiotic,
a microorganism,
and optionally the microorganism is a bacteria or a yeast,
and optionally the bacteria is a probiotic bacteria, or
a probiotic, a prebiotic, a postbiotic, or a synbiotic,
wherein optionally the prebiotic comprises a nondigestible oligosaccharide,
and optionally the nondigestible oligosaccharide comprise an inulin, a fructan, a xylose, a maltose, a mannose, or a fructooligosaccharide,
and optionally the probiotic bacteria comprise: a Bacillus or a Lactobacillus; or, a Bacillus coagulans , a Lactobacillus acidophilus , a Lactobacillus plantarum or a Lactobacillus rhamnosus,
and optionally the yeast comprises a Saccharomyces ; or a Saccharomyces boulardii.

15. The composition of claim 1 , wherein the plurality of isolated, or substantially purified intact Caudovirales bacteriophages are formulated or comprise a payload to treat, inhibit an infection,
and optionally the infection is a microbial or a bacterial infection,
and optionally the intact bacteriophages are bacteriocidal or bacteriostatic to gram negative bacteria or gram positive bacteria,
and optionally the bacteria or infection is or is caused by an MSRA infection, a Staphylococcus , a Staphylococcus aureus , a Clostridium , or a Clostridium difficile, Escherichia coli , a Shigella , a Salmonella , a Campylobacter , a Cholerae Chloerae, a Bacillus , or a Yersinia.

16. The composition of claim 1 , wherein the plurality of isolated, or substantially purified Caudovirales bacteriophages are adherent to the surface of an isolated or substantially purified: milk lipid, milk fat globule (MFG) macr

Assignees

• San Diego State Univ Sdsu Foundation
• Univ California
• The Regents Of The Univ Oe California

Inventors

• Rohwer Forest
• Barr Jeremy J
• German J Bruce

Classifications

• A61K35/76 Primary

  Viruses; Subviral particles; Bacteriophages · CPC title

• A23C7/04

  Removing unwanted substances {other than lactose or milk proteins} from milk · CPC title

• A23C9/152

  containing additives (fermented milk preparations containing additives A23C9/13) · CPC title

• A23K20/10

  Organic substances · CPC title

• A23C13/12

  Cream preparations · CPC title